👤 Schwartz GK

Title: Cytotoxic properties of rhenium(I) tricarbonyl complexes of N-heterocyclic carbene ligands. Abstract: A family of eight rhenium(I) tricarbonyl complexes bearing pyridyl-imidazolylidene or bis-imidazolylidene ligands in combination with a series of N-acetyl amino acids ligands (glycine, isoleucine, and proline) and an acetate have been synthesised and characterised. These complexes are of interest as potential anticancer agents, where the oxygen bound carboxylate ligand can exchange with water giving rise to cytotoxic cationic complexes. The pseudo-first-order aquation rate constants for the complexes were evaluated using 1H NMR time-course experiments and for the complexes of the bis-imidazolylidene ligand the average k1 value was 6.22 × 10-5 s-1 while for the pyridyl-imidazolylidene ligand the aquation rate was slower with the average k1 value being 3.00 × 10-5 s-1. Cytotoxicity studies in three cancer cell lines (MDA-MB-231, PC3 and HEPG2) showed that the Re(I) complexes of the bis-imidazolylidene ligand were significantly more toxic than those of the pyridyl-imidazolylidene ligand. Show less

Photodynamic therapy (PDT) using two-photon near-infrared light excitation is a very effective way to avoid the use of short-wavelength ultraviolet or visible light which cannot efficiently penetrate into the biological tissues and is harmful to the healthy cells. Herein, a series of cyclometalated Ir(III) complexes with a structurally simple diimine ligand were designed and the synthetic route and preparation procedure were optimized, so that the complexes could be obtained in apparently higher yield, productivity, and efficiency in comparison to the traditional methods. Their ground state and excited singlet and triplet state properties were studied by spectroscopy and quantum chemistry theoretical calculations to investigate the effect of substituent groups on the photophysical properties of the complexes. The Ir(III) complexes, especially Ir1 and Ir3, showed very low dark toxicities and high phototoxicities under both one-photon and two-photon excitation, indicating their great potential as PDT agents. They were also found to be highly sensitive two-photon mitochondria dyes. Show less

The new Ru(II) chloroquine complexes [Ru(eta(6)-arene)(CQ)Cl2] (CQ = chloroquine; arene = p-cymene 1, benzene 2), [Ru(eta(6)-p-cymene)(CQ)(H2O)2][BF4]2 (3), [Ru(eta(6)-p-cymene)(CQ)(en)][PF6]2 (en = ethylenediamine) (4), and [Ru(eta(6)-p-cymene)(eta(6)-CQDP)][BF4]2 (5, CQDP = chloroquine diphosphate) have been synthesized and characterized by use of a combination of NMR and FTIR spectroscopy with DFT calculations. Each complex is formed as a single coordination isomer: In 1-4, chloroquine binds to ruthenium in the eta(1)-N mode through the quinoline nitrogen atom, whereas in 5 an unprecedented eta(6) bonding through the carbocyclic ring is observed. 1, 2, 3, and 5 are active against CQ-resistant (Dd2, K1, and W2) and CQ-sensitive (FcB1, PFB, F32, and 3D7) malaria parasites (Plasmodium falciparum); importantly, the potency of these complexes against resistant parasites is consistently higher than that of the standard drug chloroquine diphosphate. 1 and 5 also inhibit the growth of colon cancer cells, independently of the p53 status and of liposarcoma tumor cell lines with the latter showing increased sensitivity, especially to 1 (IC50 8 microM); this is significant because this type of tumor does not respond to currently employed chemotherapies. Show less